Open AccessSIRT2 is required for efficient reprogramming of mouse embryonic fibroblasts toward pluripotency
Author(s) -
Ah-Young Kim,
Eun-Mi Lee,
Eunjoo Lee,
Jae Hong Kim,
Kyoungho Suk,
EunHye Lee,
Keun Hur,
Yean Ju Hong,
Jeong Tae,
Sunyoung Park,
KyuShik Jeong
Publication year - 2018
Publication title -
cell death and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.482
H-Index - 111
ISSN - 2041-4889
DOI - 10.1038/s41419-018-0920-3
Subject(s) - reprogramming , embryonic stem cell , microbiology and biotechnology , biology , chemistry , genetics , cell , gene
The role of sirtuins (SIRTs) in cancer biology has been the focus of recent research. The similarities between underlying pathways involved in the induction of pluripotent stem cells and transformation of cancer cells revealed the role of SIRTs in cellular reprogramming. Seven SIRTs have been identified in mammals and downregulation of SIRT2 was found to facilitate the generation of primed pluripotent stem cells, such as human induced pluripotent stem cells. Herein, we evaluated the role of SIRT2 in naive pluripotent stem cell generation using murine cells. We found that absolute depletion of SIRT2 in mouse embryonic fibroblasts resulted in a notable reduction in reprogramming efficiency. SIRT2 depletion not only upregulated elements of the INK4/ARF locus, which in turn had an antiproliferative effect, but also significantly altered the expression of proteins related to the PI3K/Akt and Hippo pathways, which are important signaling pathways for stemness. Thus, this study demonstrated that SIRT2 is required for cellular reprogramming to naive states of pluripotency in contrast to primed pluripotency states.